Prostate Cancer is the most commonly diagnosed cancer in the U.S. It is estimated that 209,900 new cases have been diagnosed in 1998; more than the number of new breast cancers. This type of cancer is the second leading cause of cancer death in men. Almost as many men died of prostate cancer in 1998(41,800) as women died of breast cancer 943,900). By age 50, as many as 4 out of 5 men have at least some cancerous cells in their prostate. Although 80 percent of these tumors are not very aggressive an d may not need any treatments, the most serious drawback o the current diagnostic methods such as PSA and histological staining is that they can not differentially diagnose fatal metastatic diseases from locally confined tumors. In the search for better molecular markers, we screened human chromosomes for tumor metastasis suppressor genes using the microcell-mediated chromosome transfer system and found that chromosome 16 encode a novel metastasis suppressor gene on its q24 region. In prostate cancer patients, the genetic abnormalities of human chromosome 16, especially at its q arm, are most frequently and consistently observed in prostate cancer. Therefore, we hypothesize that human chromosome 16 encodes a tumor metastasis suppressor gene that are capable of suppressing the metastatic process but not tumorigenesis and that the lack of functions of the gene stimulates the progression of the metastatic disease in prostate cancer patients. We propose to isolate this gene and to characterize the suppressor activity both in vivo and in vitro. We also propose to examine the status of this gene in human prostate cancer. Our long-term goal is to elucidate the functional roles of this gene in the progression of prostate cancer and to develop a diagnostic tool to accurately predict the clinical outcome of the patients.